Lesson 5, Volume 16—Evaluating and Ameliorating Dyspnea

By Michael S. Stulbarg, MD; and Virginia Carrieri-Kohlman, RN, DNSc

Objectives

1. To better understand the mechanisms of dyspnea and how they relate to causes of dyspnea.
2. To develop an approach to diagnosis of dyspnea that recognizes its very broad differential diagnosis and the remarkable number of tools that may be helpful in diagnostically evaluating this symptom.
3. To understand the approaches available for thesymptomatic treatment of dyspnea, even when treatment options for of the underlying disease(s) have been exhausted.

Key words

dyspnea; mechanisms; treatment

What Is Dyspnea?

Dyspnea is a clinical term for shortness of breath or breathlessness, ie, the discomfort associated with effort in breathing or the urge to breathe. Dyspnea may be considered part of the warning system for humans to recognize when they are at risk of receiving inadequate ventilation. For example, a blunted perception of dyspnea may put asthmatics at greater risk of fatal attacks.¹ Dyspnea is a frequent cause of emergency room visits,² is an independent predictor of mortality,³ and has been found to be more related to quality of life than are pulmonary function tests.⁴

A recent consensus statement from the American Thoracic Society⁵ offered the following definition of dyspnea: "Dyspnea is a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social and environmental factors, and may induce secondary physiological and behavioral responses." The key point of this definition is that dyspnea is subjective and therefore is variable among individuals with apparently similar degrees of impairment. This may explain the Social Security Administration’s reluctance to utilize dyspnea ratings in the determination of disability.

Dyspnea occurs in healthy individuals (for example, with exercise or at high altitude), but it is experienced by respiratory patients at lower levels of physical exercise or altitude. Moreover, dyspnea is distinct from the specific physical signs we associate with it, such as the use of accessory muscles or pursed-lips breathing. Dyspnea is especially important when it interferes with activities of daily living. Dyspnea is increasingly important as an outcome measure in studies of cardiac and pulmonary patients, especially in relation to medication effects⁶ and the impact of exercise training.^7-9

Mechanisms of Dyspnea

Dyspnea is experienced in the part of the cerebral cortex responsible for sensory perception. The key concept in understanding the mechanism of dyspnea is that it does not occur just because there is active chest movement (as in voluntary hyperventilation), but it requires stimulation of the respiratory center as occurs with, hypoxia, hypercapnia, metabolic acidosis, or exercise.^5,10-12 With any of these stimuli, ventilation increases until a threshold is reached, beyond which dyspnea is first sensed subjectively by the individual. With further stimulation, ventilation rises and dyspnea increases. However, even among those unable to increase ventilation (for example, those with spinal cord injury), respiratory stimulation by elevation of PaCO₂ will still result in subjective dyspnea.¹³

As a subjective experience, dyspnea may be greatly affected by the situation in which it occurs (eg, the sensation may be regarded as mild or unimportant if it is expected, as when hiking at high altitude). Mood or psychological state, especially anxiety, may significantly affect the experience of dyspnea. Dyspnea does not usually limit maximal exercise in healthy subjects, except at high altitude or at extraordinary levels of performance. In contrast, patients with chronic lung disease may be required to use much of their ventilatory reserve at low levels of exertion and thus be prevented from reaching normal levels of exercise.¹⁴

Interaction of multiple factors may determine the severity of dyspnea. For example, under controlled experimental conditions, subjects with asthma and airway obstruction will experience a greater degree of dyspnea at any given level of ventilation at baseline than following bronchodilators, even if their actual minute ventilation is the same. Greater respiratory effort is required in face of bronchoconstriction, such that the "drive" to breathe must be greater to overcome the obstruction to flow. This extra effort appears to be experienced in the brain as greater dyspnea. Similarly, in the face of hyperinflation, respiratory muscles are mechanically disadvantaged, and the "effort" of breathing is greater, again requiring greater respiratory drive. With bronchodilators that reduce hyperinflation, dyspnea may improve, even in the absence of improvement in airflow. There is also evidence that inflammation in the airway mucosa of asthmatics may directly affect dyspnea, apart from any effect on airflow.¹⁵ Obesity is another factor that can affect the severity of dyspnea.¹⁶ Obesity increases metabolic demands while at the same time increasing the work of moving the chest wall and diaphragm.

As opposed to airway obstruction, the dyspnea of severe heart disease or pulmonary hypertension is as well recognized, but difficult to explain. While dyspnea in states of low cardiac output may occur because of early onset of lactic acidosis with exercise, the dyspnea of pulmonary hypertension occurs before there is any significant acidosis. It is therefore likely that there are receptors in the great vessels that are pressure sensitive and result in stimulation of ventilation and dyspnea. Although receptors in the lungs themselves may be important for dyspnea, patients with bilateral lung transplantation who have lost the nerves of their lung can still experience dyspnea.¹⁷

Measurement of Dyspnea

Dyspnea, like pain, is a qualitative sensation that nonetheless can be measured. Measurement of dyspnea is important for research into its mechanisms and its treatment. However appealing such measurements are for research purposes, they are not yet widely used by physicians to monitor dyspnea in clinical practice. Unlike pain, there are physiologic measures such as pulmonary function and exercise testing that are presumed to reflect the severity of dyspnea. These measures, however, may either underestimate or overestimate the impact of lung disease on symptoms. This underscores the importance of measuring the subjective symptom itself.

Dyspnea can be measured with simple word scales and these have been widely used for epidemiologic surveys. Dyspnea can be rated in relation to specific activities in real time or retrospectively using any of many available scales: visual analog scale (a 10-cm line to represent a scale from 0 to 100 ["no dyspnea" to "maximal dyspnea"]), simple numerical 0-to-10 scale ("none" to "worst imaginable"), word scale (Table 1), or a scale combining words and numbers (the Borg scale; Table 2).¹⁰

Such quantification allows evaluation of change over time, especially in response to interventions such as medications or exercise training. Patients can also be taught to use levels of dyspnea to guide their physical activities.

It has been suggested that the words that individual patients use to describe their dyspnea may relate to their underlying pathophysiology. With exercise, most subjects use "effort" and "heaviness" to describe their breathing. Patients with either COPD or interstitial lung disease are likely to choose "increased inspiratory difficulty" and "unsatisfied inspiratory effort" to describe their breathing. Obstructed patients tended to describe their breathing as "shallow," while those with interstitial lung disease report "rapid breathing." Unfortunately, these differences are not distinct enough to help with diagnosis in individual patients. This topic is further complicated by cross-cultural aspects of language use. Recent research suggests that there may be important differences among ethnic groups in choices of words to describe respiratory discomfort or dyspnea. In one study of asthmatics, African-Americans used primarily upper-airway word descriptors (eg, "tight neck"), while whites used lower-airway or chest-wall word descriptors.¹⁸ Failure to recognize these distinctions may lead to important underestimation of disease severity. It is worth noting that even patients with severe lung disease may report that they are more limited by "fatigue" or "leg fatigue" than by dyspnea.

Differential Diagnosis for Causes of Dyspnea

Dyspnea is a nonspecific symptom of any disease involving the respiratory system. While diseases of the lungs, chest wall, pleura, diaphragm, upper airway, and heart are most common, diseases of many other organ systems (eg, neuromuscular, skeletal, renal, endocrine, rheumatologic, hematologic, and psychiatric) may involve the respiratory system and present with dyspnea. The focus here is on general principles leading to a proper diagnosis rather than a detailed description of the features of each of these disorders.

Conceptually, diseases provoking dyspnea may affect the respiratory system in several ways: mechanical limitation of the lungs or chest, increased stimulation of breathing, relative or absolute weakness of the ventilatory muscle apparatus, and psychogenic causes (Table 3). Indeed, many diseases may cause dyspnea by more than one mechanism. For example, pleural effusion may cause relative hyperinflation of the chest with less effective respiratory muscle function, hypoxemia by ventilation-perfusion mismatch, and reduced lung expansion (ie, restriction). Asthma may cause dyspnea by obstruction of airways, hyperinflation, hypoxemia, anxiety, and airway inflammation. Coronary artery disease may cause interstitial edema, pleural effusion, and premature lactic acidosis. Multiple processes may interact to cause dyspnea. For example, patients with COPD may also have coronary artery disease. Fear and anxiety or involvement in litigation may accentuate dyspnea of any cause. Patients who think their lungs have been injured by external factors, such as toxins, may report more dyspnea than patients with similar degrees of lung dysfunction.¹⁹

The initial approach to diagnosis of dyspnea is usually determined by the acuity of the symptom. Acute dyspnea may suggest potentially life-threatening involvement of the heart or lungs (eg, asthma, pulmonary embolism, pneumonia, pneumothorax, myocardial infarction). Once these urgent problems are excluded, the pace of evaluation may be slower and similar to that for subacute or chronic dyspnea. The diagnostic approach to dyspnea may be thought of in terms of disease with mechanical limitations on the respiratory system, diseases with increased drive to breathe, and diseases affecting the central perception of the symptom. Many diseases (eg, asthma) fall into more than one category. In the search for a diagnosis, one may eventually do tests to look for evidence of disease affecting all known mechanisms.

Work-up of Dyspnea

A comprehensive history and physical examination are required for diagnosis of dyspnea (Table 4). Key questions relate to the persistence or variability of the symptom, aggravating factors (ambulation, eating, position, exposures), and medications or activities (such as position) that help relieve the symptoms. For example, intermittent dyspnea may be due to asthma or heart failure, while persistent or progressive dyspnea suggests other chronic conditions, such as chronic obstructive pulmonary disease, interstitial fibrosis, pulmonary hypertension. Dyspnea may occur in conditions when ventilation is stimulated by lactic acid production at relatively low levels of exercise (deconditioning, anemia, or low cardiac output states). Nocturnal dyspnea is typical of asthma, congestive heart failure, gastroesophageal reflux, or even nasal obstruction. As activity generally accentuates dyspnea of physiologic origin, dyspnea occurring independent of physical activity suggests allergic, mechanical (particularly reflux), or psychological problems. Dyspnea coming on after exercise suggests exercise-induced asthma. Obesity may aggravate dyspnea because of both the effort of moving the extra weight and increased metabolic demand. Cachexia may result in loss of muscle mass and respiratory muscle weakness. Sleep-disordered breathing may interact with other problems to increase dyspnea. Symptoms of systemic congestion (eg, pitting edema, abdominal swelling) may suggest right ventricular failure of any cause (eg, pulmonary hypertension, obstructive sleep apnea, or left ventricular failure). Raynaud’s phenomenon as well as skin, joint, or swallowing problems may suggest collagen vascular disease. Although emotions may affect dyspnea of any cause, psychogenic dyspnea should be suspected when dyspnea varies greatly and is unrelated to physical activity.

The focused cardiopulmonary examination should assess multiple factors. Cough on inspiration or expiration may suggest obstructive or interstitial lung disease. Decreased chest expansion may occur in both restriction and severe hyperinflation, but the chest shape would be quite different (ie, increased in emphysema.) A decrease in the intensity of the breath sounds may suggest emphysema, pneumothorax, or pleural effusion, although concomitant dullness would suggest effusion. Forced expiration may uncover focal or diffuse wheezing. The cardiac examination may suggest pulmonary hypertension (eg, right ventricular heave, increased pulmonic sound) or right ventricular failure (eg, jugular venous distention, hepatojugular reflux, pedal edema). It is always important to remember that the most common cause of right heart failure is left heart failure. General physical examination may provide vital clues to diagnosis: respiratory rate, body habitus (eg, cachexia, obesity), posture, use of pursed lips, use of accessory muscles, and psychological affect are all relevant in this regard. Clubbing may be associated with many processes, notably cancer. Lower-extremity edema suggests congestive failure if symmetrical, and venous thrombosis if asymmetrical.

Although the laboratory values often are not helpful in the diagnosis of the causes of dyspnea, the database should include a hemogram, electrolytes, and creatinine. Anemia may be a clue to occult bleeding or serious systemic problems. Polycythemia may suggest chronic hypoxemia. Elevation of the sedimentation rate may suggest occult inflammation in the lungs, but is insensitive for inflammatory disease of the interstitium. Renal failure may present as dyspnea of unknown cause due to anemia and/or metabolic acidosis. The database should also include a plain chest radiographic assessment. Classical findings that are of help include hyperinflation, parenchymal infiltration, and pleural disease. Less obvious findings may include early findings of interstitial lung disease (eg, decreases in lung volume or subtle increases in lung density). Though the yield of "routine" ECG is low, it may reveal previously unsuspected coronary artery disease or even pulmonary hypertension (ie, signs of right ventricular hypertrophy or strain).

Special Studies in Dyspnea

Although pulmonary function tests may be diagnostic, the degree of abnormality in tests of respiratory function correlates only moderately with severity of dyspnea. Spirometry, including FEV₁ and FVC, are excellent screening tests for both obstructive and restrictive disease, although both may be normal despite significant asthma or interstitial fibrosis. Flow-volume loops are particularly helpful for assessing obstruction, as the shape of the loop may distinguish upper airway obstruction from the more common problems of COPD and asthma. As airway obstruction in asthma may be intermittent, peak flow monitoring with a portable meter at times of dyspnea at home or in the workplace may be more useful than tests in the laboratory. Pulse oximetry is a reasonable screen for hypoxemia and serum bicarbonate for chronic hypercapnia.

Cardiopulmonary exercise testing may indicate whether exercise is limited by the pulmonary or cardiovascular system (or even some unrelated problem such as leg pain or fatigue).²⁰ A broad array of other studies may be helpful. Spiral CT scanning of the chest with iodinated contrast is gradually replacing ventilation-perfusion lung scanning as the screening procedure of choice for the diagnosis of pulmonary embolic disease.²¹ Gallium and high-resolution CT scanning are sensitive, but not specific for occult infectious (eg, Pneumocystis carinii) and inflammatory (eg, interstitial pneumonitis) lung disease. If exercise testing suggests cardiac dysfunction, echocardiography (preferably combined with supine exercise), radionuclide scanning, or cardiac catheterization may identify unsuspected wall-motion abnormalities, valvular disease, or pulmonary hypertension. Bronchoscopy (with or without biopsy) is almost never used as a screening test for dyspnea, but may be crucial if pulmonary function studies suggest upper airway obstruction or if imaging studies show parenchymal lung disease.

If dyspnea is clearly unrelated to exercise, and especially if it increases with medical attention or emotional distress, psychological consultation should be sought. Patients with chronic lung disease are prone to anxiety and symptoms of panic and patients with panic disorder may present with dyspnea as a primary symptom.²²

Treatments for Dyspnea

General Interventions

The key to treatment of dyspnea is to optimize treatment of the underlying disease and its complications. Discussion of specific treatments is beyond the scope of this review. The major complications of chronic lung disease that contribute to dyspnea include hypoxemia, respiratory failure (ie, hypercapnia), anemia, pleural effusion, and recurrent respiratory infection. Treatment should focus on all the relevant factors in an individual patient.

Oxygen

Oxygen has been shown to be the most effective treatment for COPD, prolonging life and relieving dyspnea. Oxygen usually decreases respiratory drive and minute ventilation but may also improve diaphragmatic function and reduce pulmonary hypertension. Although controlled data are limited, the same principles are used to guide oxygen therapy for other kinds of chronic lung disease. Not all dyspneic patients are hypoxemic, and oxygen is usually not indicated in the absence of "severe" hypoxemia (ie, PaO₂ < 56 mm Hg or PaO₂ < 60 mm Hg in the presence of cor pulmonale and/or polycythemia). Oxygen should be titrated to keep PaO₂ > 60 mm Hg, although this is commonly done with pulse oximetry aiming for an oxygen saturation of 92 to 96% at rest. Flow rates may be arbitrarily increased by 1 L/min with exercise, although it is preferable to titrate the oxygen to assure adequate oxygenation with exertion. Oxygen-conserving devices (ie, reservoir devices or inspiratory demand devices) prolong the useful life of portable oxygen containers between fills, thus allowing greater patient mobility. Although many patients report that oxygen relieves dyspnea in the absence of severe hypoxemia, most third-party payers will not cover the expense.

Ventilatory Support

Hypercapnia is common in patients with advanced obstructive disease and is usually not treated specifically, even though selected patients may respond to partial ventilatory support with nocturnal mask ventilation. In contrast, such partial ventilatory support may be dramatically helpful for dyspnea in patients with neuromuscular or chest-wall problems (eg, myopathies or spinal deformities). Treatment of anemia, especially when due to a reversible cause such as iron deficiency, may substantially ameliorate dyspnea. There are limited data supporting the value of treating inflammation in order to reduce dyspnea. This may explain some of the benefit of inhaled steroids in patients with chronic obstructive disease and of antibiotics in those with chronic bronchiectasis. Improvement in mechanical factors that affect chest movement may substantially improve dyspnea. This is best illustrated by the impact of thoracentesis of large effusions and completion of pregnancy. Weight loss in obese patients may ameliorate dyspnea of any cause by decreasing the effort of breathing as well as the metabolic demands of physical activity. In contrast, weight gain in cachectic patients may improve respiratory muscle strength and decrease the sense of effort in breathing.

Pulmonary Rehabilitation

Dyspnea may continue to be an incapacitating symptom despite optimal treatment of the underlying disease and its complications. In such situations, the treatment of dyspnea demands compassion, comparable to the treatment of pain in a patient with end-stage malignancy. The general approach to treatment is to focus on (1) reducing ventilatory demand, (2) improving respiratory muscle function, and (3) modifying the central perception of dyspnea. The best overall approach to treatment of dyspnea includes pulmonary rehabilitation, a multimodality approach using personnel trained to teach patients about their disease and its treatments.²³ Dyspnea may be ameliorated with conservative approaches such as pacing activities, pursed-lip breathing, relaxation, or panic control. Although most research has been carried out in patients with COPD, other types of patients (eg, those with interstitial disease) are also likely to benefit.²⁴ Such teaching is combined with exercise of whatever kind the patient can do combined with emotional support on an individual or group basis. Numerous controlled trials have demonstrated the value of such programs for symptom control and quality of life.⁹ Even exercise alone without education or group interaction has been shown to improve dyspnea and quality of life.²⁵ Repeated exercise may result in desensitization to the symptom, ie, less dyspnea following the same stimulus.²⁶ Desensitization may be especially important, as it may play a role even if exercise performance does not improve. Even though exercise in formal rehabilitation may be preferable, exercise at home or in exercise facilities is much more practical for many individuals. Most exercise programs include some stretching and weightlifting (especially for upper extremity activities), as well as aerobics. It is important to continue exercise after completing such programs, and especially after an exacerbation of disease. Although patients may be hesitant to bring the subject up, strategies to decrease dyspnea during sexual activity may be particularly helpful (eg, medications before sexual relations, use of supplemental oxygen, timing before meals, and choosing less demanding positions for the partner with lung disease).

Opiates

Opiates can relieve dyspnea by depressing respiratory drive and changing the patient’s perception of his or her dyspnea. Although physicians are anxious to relieve dyspnea, fear of respiratory depression and criticism by their colleagues has discouraged them from using opiates, even in treating those with end-stage disease. In addition, none of the controlled studies in nonmalignant lung disease has shown a consistent benefit for dyspnea, and adverse effects have been frequent.²⁷ In contrast, many studies have shown the value of opiates for dyspnea in terminal patients with malignancy.²⁸ There has been considerable interest in the use of inhaled opiates for relief of dyspnea without systemic effects, but the available data are not persuasive.²⁹

Pending additional data, opiates should be used with compassionate caution in patients with end-stage nonmalignant lung disease, recognizing that it may be appropriate to risk respiratory depression in exchange for relief of what may be a terribly distressing symptom. Despite the fact that anxiety and depression may be important problems for patients with chronic lung disease, there is only limited evidence that anxiolytics or antidepressants may help control dyspnea. If an anxiolytic is to be tried, it is preferable to use an agent which produces little or no respiratory depression (eg, buspirone).

Lung Volume Reduction Surgery

The advent of lung volume reduction surgery for relief of dyspnea in advanced emphysema (but not other forms of COPD) deserves special mention. Removal of multiple bullous or emphysematous portions of the lungs reduces the size of the lungs and improves lung recoil. A large, multicenter, controlled trial is currently underway in the United States. Multiple reports have documented that improvement in pulmonary function and dyspnea may occur in some patients.³⁰ Amelioration in dyspnea may be explained by the combination of decreased hyperinflation, improved FEV₁, and often improvement in hypoxemia. Although these changes may last for only a few years, search for relief of suffering from dyspnea has led many patients to undergo this surgery, often at their own expense.

Summary

Dyspnea may be caused by diseases in virtually any organ system, whether due to interference with breathing, increased demand for breathing, or effective weakening of the respiratory "pump." Diagnosis of dyspnea requires a comprehensive database that will uncover many of the causes. When the cause is not obvious, a series of imaging and functional studies usually uncover a specific diagnosis. Sophisticated studies of the heart, pulmonary vascular bed, and lung parenchyma may be necessary. Psychogenic or behavioral dyspnea should be considered only after detailed clinical evaluation. Treatment of dyspnea is most effective when based on a specific diagnosis. When treatment of the underlying disease and its complications is inadequate for relief of dyspnea, treatment should focused on the symptom per se. In advanced disease, compassion may require the use of agents that may actually depress respiratory function.

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